Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients - Full Text View

Sponsored by:	AM-Pharma
Information provided by:	AM-Pharma
ClinicalTrials.gov Identifier:	NCT00509938

Purpose

The safety and tolerability of hLF 1-11 has to be established first in HSCT recipients who are at risk of developing, but have not yet developed, infectious complications due to invasive fungal disease. These patients are different from healthy volunteers because they have received myeloablative treatment which not only arrests haematopoiesis resulting in neutropenia but also induces mucosal barrier injury both of which predispose to infections which typically occur during the week after transplant. It is therefore essential to know that hLF 1-11 is when given during neutropenia and mucosal barrier injury before infections ensue

Condition	Intervention	Phase
Hematopoietic Stem Cell Transplantation Bacterial Infections and Mycoses	Drug: human lactoferrin peptide 1-11	Phase I Phase II

MedlinePlus related topics: Bacterial Infections Fungal Infections

Drug Information available for: Lactoferrin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Safety and Efficacy of Human Lactoferrin hLF1-11 for the Treatment of Infectious Complications Among Haematopoietic Stem Cell Transplant Recipients Part A: Clinical Study Protocol SC12: Safety of a Single Dose of 5 mg of hLF1-11 Given to Autologous Haematopoietic Stem Cell Transplant Recipients

Further study details as provided by AM-Pharma:

Primary Outcome Measures:

Safety and tolerability by recording the vital signs, clinical chemistry, local tolerability and adverse events during the study [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

formation of antibodies anti-hLF 1-11 during the study. [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]

Enrollment:	8
Study Start Date:	March 2006
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 5mg hLF1-11, single dose iv	Drug: human lactoferrin peptide 1-11 Each subject will receive a single intravenous dose of hLF1-11 given in a volume of 20mL given over 20 minutes i.e. 1mL/per minute.

Detailed Description:

Background:

Human lactoferrin (hLF) is a glycoprotein containing 692 amino acids and found in the saliva, milk, tears, and other body fluids. Peptide representing the first cationic domain, i.e. a peptide comprising the first eleven residues of hLF (further referred to as hLF1-11) was significantly more effective than the full length hLF or the peptide representing the second cationic domain in killing a variety of bacteria in vivo. The mechanism of action comprises a number of independent factors. The classical way to explain the efficacy is the direct killing effect, which typically is observed in vitro at relatively high concentrations. The results of in vitro and in vivo experiments suggest that the mechanism of action is predominantly through the intermediary of cells and/or components of the host as opposed to a direct interaction with the pathogen.

The objective is to develop hLF1-11 as an effective and safe antibacterial and antifungal for the treatment of fungal and bacterial infections that develop during the neutropenia that results from myeloablative therapy to prepare for a haematopoietic stem cell transplant (HSCT) formerly referred to as bone marrow transplant. Rates of infection and related morbidity are high in this population making it an attractive target for testing clinically the proof-of-principle that hLF1-11 can provided effective treatment. Subsequently, hLF1-11 will be developed further as a systemic antifungal agent.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

admitted for an autologous HSCT after myeloablative therapy with high-dose melfalan
managed with a 4-lumen central venous catheter
BMI <30
able and willing to participate
has provided written informed consent
there is no medical reason for exclusion
has adequate renal function (creatinine <110 µmol/L (man); <90 µmol/L (woman))
has adequate liver function (ASAT <40 U; ALAT <45 U; bilirubin <10µmol/L)
has no known allergy to lactoferrin
has no history of hepatitis and is not HIV seropositive
if a woman, functionally post-menopausal

Exclusion Criteria:

A history of, or presence of, significant respiratory, cardiovascular, neurological, haematological, endocrine, gastrointestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs (as judged clinically relevant by the investigator).
Participation in a study with a new chemical entity or new molecular entity 3 months before or participation in a study with a registered drug less than 5 times of the half life of the registered drug before entering the study.
A clinically relevant history of intolerance or hypersensitivity to the study drug, or its additives and excipients in the intravenous formulation.
Evidence of having serum hepatitis or carrying the hepatitis B surface antigen or Hepatitis C antibodies or being HIV positive.
Subjects, who in the opinion of the investigator should not, for reasons of safety, participate in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509938

Locations

Netherlands, Gelderland
UMC St. Radboud
Nijmegen, Gelderland, Netherlands, 6500 HB

Sponsors and Collaborators

AM-Pharma

Investigators

Principal Investigator:

J.P. Donnelly, PhD

UMC St. Radboud Nijmegen, The Netherlands

More Information

Responsible Party:	AM-Pharma ( Jacques Arend MD, VP Medical Development )
Study ID Numbers:	AMP 02-01, SC12, IS 044096
Study First Received:	July 31, 2007
Last Updated:	October 16, 2008
ClinicalTrials.gov Identifier:	NCT00509938
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by AM-Pharma:

immunocompromized
hLF1-11
antimicrobial
peptide
lactoferrin

Study placed in the following topic categories:

Bacterial Infections
Mycoses

ClinicalTrials.gov processed this record on January 16, 2009